POS0427 PRE-INFLAMMATORY MESENCHYMAL (PRIME) CELLS IDENTIFIED BY MASS CYTOMETRY IN THE PERIPHERAL BLOOD OF PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS
Authors: E. K. Vetsika, M. Chatzopoulos, G. E. Fragoulis, M. Tektonidou, G. Kollias, P. Sfikakis
Journal: Annals of the Rheumatic Diseases (2022)

Background Experimental evidence suggests that synovial fibroblasts (SFs) may play a central pathogenetic role in chronic inflammatory arthritis in humans. RNA of the mesenchymal marker cadherin-11 characterising SFs is overexpressed in the peripheral blood of rheumatoid arthritis (RA) patients compared to healthy donors and correlates with established polyarthritis [1]. Recently, Orange et al. using RNA sequencing and flow cytometry have identified in the peripheral blood of RA patients PRIME (PRe-Inflammatory MEsenchymal) cells, considered as the precursors to inflammatory sublining SFs, that could be used as predictors of RA flares [2]. Objectives To test the hypothesis that circulating PRIME cells can be identified by mass cytometry in patients with active RA, as well as in patients with active psoriatic arthritis (PsA). Methods The expression of markers suggestive of PRIME cells, namely, cadherin-11 and/or podoplanin (both expressed on SFs), and/or CD90 (Thy-1, expressed on sublining SFs), and/or Notch-3 (expressed on endothelial cells and sublining SFs), and/or CD34 (expressed on stem cells and SFs) was evident in all 10 RA and 5 PsA-derived blood samples. Circulating PRIME cell levels were elevated in patients (0.019%±0.003%) than healthy donors (0.008%±0.002%, p =0.004). The increased PRIME cell levels were more pronounced in PsA (0.023%±0.007%, p =0.003) than RA (0.017%±0.003%, p =0.03), when compared to healthy donors. PRIME cells were also present in 2 RA synovial fluid samples, being at three-fold higher levels than in the paired blood samples. Interestingly, a fraction of circulating PRIME cells exhibited expression of HLA-DR, suggestive of antigen-presenting capacity. Results The expression of markers suggestive of PRIME cells, namely, cadherin-11 and/or podoplanin (both expressed on SFs), and/or CD90 (Thy-1, expressed on sublining SFs), and/or Notch-3 (expressed on endothelial cells and sublining SFs), and/or CD34 (expressed on stem cells and SFs) was evident in all 10 RA and 5 PsA-derived blood samples. Circulating PRIME cell levels were elevated in patients (0.019%±0.003%) than healthy donors (0.008%±0.002%, p =0.004). The increased PRIME cell levels were more pronounced in PsA (0.023%±0.007%, p =0.003) than RA (0.017%±0.003%, p =0.03), when compared to healthy donors. PRIME cells were also present in 2 RA synovial fluid samples, being at three-fold higher levels than in the paired blood samples. Interestingly, a fraction of circulating PRIME cells exhibited expression of HLA-DR, suggestive of antigen-presenting capacity. Conclusion Rare circulating mesenchymal cells with antigen-presenting properties may be of pathogenetic importance in patients with RA and PsA. Whether their measurement is clinically relevant, as well their function during chronic inflammatory arthritis, merits further studies. References [1]Sfikakis PP, Christopoulos PF, Vaiopoulos AG, et al. Cadherin-11 mRNA transcripts are frequently found in rheumatoid arthritis peripheral blood and correlate with established polyarthritis. Clinical Immunology, 2014,155(1):33–41. [2]Orange DE, Yao V, Sawicka K, Fak J, et al. RNA Identification of PRIME cells predicting rheumatoid arthritis flares. New Engl J Med, 2020,383(3):218. Acknowledgements We acknowledge support of this work by the project “The Greek Research Infrastructure for Personalised Medicine (pMedGR)” (MIS 5002802) which is implemented under the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union (European Regional Development Fund). Disclosure of Interests None declared.